Neovessels play a critical role in homeostasis, regeneration, and pathogenesis of tissues and organs1-2, and their spatial organization is a major factor to influence the vascular function3. It has been proposed that an ability to control growth direction and spacing of neovessels over physiologically relevant lengths ranging from about 100 μm to about 500 μm can provide a better understanding and controllability of neovessel formation3-7. However, a technology to accomplish this challenging goal is still lacking.
Prior studies have demonstrated that spatiotemporal distribution of multiple proangiogenic growth factors in a 3D tissue can control growth direction of neovessels and also their macroscale spacing7-8. In these studies, various polymeric scaffolds were assembled by welding a growth factor-releasing layer with a growth factor-free layer, while varying layer thickness at the millimeter scale. To further control spatial organization of the neovessels at a length scale required to uniformly perfuse 3D tissue, various micropatterning, ink-jet printing and microfluidic techniques were used to control spatiotemporal distribution of proangiogenic factors or direct the adhesion pattern of endothelial cells at micrometer scales9-15. However, there have been no reports of regulating the microscale spacing between functional neovessels, through which blood flows in vivo, using microfabrication techniques. Spacing of neovessels is important for proper vascularization of tissue.